Oxygen (O2) toxicity is the metabolic, stuctural and/or functional derangement in an organ resulting from exposure to elevated O2 concentrations. Because the lungs are exposed to O2 tensions higher than those in any other vital organ, pulmonary O2 toxicity is the principal factor limiting the safe and effective use of O2. The precise molecular mechanisms by which high partial pressures of O2 exert a toxic effect are not known. Thus, there is no reliable method to prevent pulmonary O2 toxicity in man other than keeping the inspired O2 concentration below the toxic level. Recent evidence indicates that the superoxide anion (O2-), an extremely potent free radical which is produced by a number of biologically important metabolic reactions, plays an integral role in the pathogenesis of O2 toxicity. The primary defense against O2- appears to be an enzyme, superoxide dismutase (SOD), which catalyzes the dismutation of O2- to less toxic forms. This enzyme is an efficient catalyst which is ubiquitous among O2 metabolizing cells. Raising the concentration of O2 induces increased accumulation of SOD in microorganisms and cells which contain high concentrations of SOD are more resistant to high partial pressures of O2. Thus it seems likely that SOD plays a key role in protecting cells from the toxic effects of O2. The objective of the proposed project is to evaluate a variety of dosages and therapeutic schedules of SOD to; (1) protect against the development of pulmonary O2 toxicity and (2) facilitate recovery from pulmonary O2 toxicity, O2 toxicity will be evaluated by lung morphology and measurement of pulmonary clearance of serotonin. Depression of lung serotonin clearance has been shown previously to be a sensitive metabolic index of lung O2 poisoning. The proposed project will provide information regarding the role of SOD in the therapy of pulmonary O2 toxicity, and it will provide information regarding the role of SOD in the therapy of pulmonary O2 toxicity, and it will provide insights into the role of O2- in the pathogenesis of pulmonary O2 toxicity.